It has been, and will continue to be, the major objective of this program to elucidate mechanisms underlying hemolytic disorders in humans especially as they may relate to abnormalities in the red cell membrane. Three specific areas of investigation will continue to be pursued: 1) further elucidation of the abnormality in red cell membrane protein in hereditary spherocytosis will be attempted; that such an abnormality exists has been shown by the principal investigator; it is now our hope to more fully characterize the abnormality biochemically, and to use our findings, if possible, to gain understanding into the pathogenesis of other dominantly-inherited genetic disorders; 2) the possible deleterious effects of abnormal plasma environments on the membrane and intracellular metabolism of blood cells will be investigated. It is especially our aim to investigate the effects on blood cell homeostasis of hypophosphatemia and hyperglycemia. 3) the possible effects on red cell function of the ionic environment will be investigated; we are especially interested in evaluating whether plasma calcium alterations may play a role in the painful crises which plague patients with sickle cell anemia; 4) finally, the role of activated complement in causing margination of granulocytes in pulmonary capillaries will be investigated.